Full-length characterization of A1/D intersubtype recombinant genomes from a therapy-induced HIV type 1 controller during acute infection and his noncontrolling partner

Abstract

To increase the understanding of mechanisms of HIV control we have genetically and immunologically characterized a full-length HIV-1 isolated from an acute infection in a rare case of undetectable viremia. The subject, a 43-year-old Danish white male (DK1), was diagnosed with acute HIV-1 infection after 1 year in Uganda. Following transient antiretroviral therapy DK1 maintained undetectable viral load for more than 10 years. His Ugandan wife (UG1) developed high viral load. HIV-1 sequences from both individuals were compared by bootscanning for recombination break points. Diversity plots and phylogenic trees were constructed and diversity and evolutionary distances were calculated. Intracellular IFN-gamma in CD8(+)CD3(+) T-lymphocyte reactions was investigated by intracellular flow cytometry (IC-FACS). Virus isolates from both patients were A1D intersubtype recombinants showing 98% sequence homology in shared regions. Four of seven crossover points were identical; however, the env gene from UG1 was subtype D, but A1 in DK1. Both viruses encoded proteins of the expected length and replicated equally well in vitro. DK1 and UG1 shared the HLA-A02 tissue type. HLA-A02-restricted CD8(+) T cell IFN-gamma IC-FACS response in DK1 was detected against only one (Pol(476)) of 23 conserved epitopes. Neutralizing antibodies were induced only to the homologous isolate. These results indicate an A1D intersubtype recombination or transmission of a minor variant. Transient early antiretroviral therapy may have induced full HIV-1 control in this individual mediated by a narrow specific cytotoxic T lymphocyte and neutralizing antibody response and/or other factors yet to be characterized.